Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients
Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients
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激活的诱导共刺激剂阳性程序性细胞死亡 1 阳性滤泡辅助 T 细胞表明溃疡性结肠炎患者的疾病活动度和严重程度
DOI：
10.1111/cei.13485
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发表时间：
2020-07-28
影响因子：
4.6
通讯作者：
Liu, Chen
中科院分区：
文献类型：
--
作者：
Long, Y.;Zhao, X.;Liu, Chen
诱导性共刺激分子阳性（ICOS）和程序性细胞死亡蛋白1阳性（PD - 1）是滤泡辅助性T细胞（Tfh）的重要标志物；然而，它们在溃疡性结肠炎（UC）中的作用及临床价值仍不明确。在本研究中，我们招募了68例UC患者和34名健康对照者。通过流式细胞术分析循环中的ICOS⁺、PD - 1⁺以及ICOS⁺PD - 1⁺ Tfh细胞亚群。对12例经5 - 氨基水杨酸治疗后达到缓解的活动期UC患者进行随访，并分析Tfh细胞亚群的变化。同时分析血清免疫球蛋白（Ig）G、C反应蛋白（CRP）、白细胞介素（IL） - 4和IL - 21水平以及B细胞亚群，并计算梅奥评分。对Tfh细胞亚群与各项临床指标进行相关性分析。绘制受试者工作特征（ROC）曲线以评估Tfh细胞亚群对疾病监测的效能。我们发现，活动期UC患者中ICOS⁺、PD - 1⁺以及ICOS⁺PD - 1⁺ Tfh细胞水平显著升高，而在达到临床缓解时显著降低。活化的ICOS⁺PD - 1⁺ Tfh细胞与血清CRP及梅奥评分呈正相关。此外，ICOS⁺PD - 1⁺ Tfh细胞与循环中的新记忆B细胞、浆母细胞以及血清IgG、IL - 4和IL - 21显著相关。ROC分析显示，当ICOS⁺PD - 1⁺ Tfh细胞与PD - 1⁺ Tfh细胞联合使用时，区分活动期UC患者与病情稳定缓解患者的诊断效能高于单独使用其中任何一种，曲线下面积（AUC）值为0.931。我们的研究结果表明，在UC发病机制中，增多的ICOS⁺PD - 1⁺ Tfh细胞与B细胞活化相关，且可能是UC疾病监测的潜在生物标志物。
Inducible co-stimulator-positive (ICOS) and programmed cell death 1-positive (PD-1) are important markers for follicular helper T cells (Tfh); however, their roles and clinical values in ulcerative colitis (UC) remain unknown. In this study, we recruited 68 UC patients and 34 healthy controls. Circulating ICOS+, PD-1(+)and ICOS+PD-1(+)Tfh subsets were analyzed by flow cytometry. Twelve active UC patients achieving remission after treatment with 5-aminosalicylic acid were followed-up and Tfh subset changes were analyzed. Serum immunoglobulin (Ig)G, C-reactive protein (CRP), interleukin (IL)-4 and IL-21 levels and B cell subsets were analyzed and Mayo scores were calculated. Correlation analyses were performed between Tfh subsets and the clinical indicators. Receiver operating characteristic (ROC) curves were generated to evaluate the efficiency of Tfh subsets for disease monitoring. We found that levels of ICOS+, PD-1(+)and ICOS+PD-1(+)Tfh cells were significantly increased in active UC and significantly decreased when achieving clinical remission. Activated ICOS+PD-1(+)Tfh cells were positively correlated with serum CRP and Mayo scores. Furthermore, ICOS+PD-1(+)Tfh cells were significantly correlated with circulating new memory B cells and plasmablasts, as well as serum IgG, IL-4 and IL-21. ROC analyses showed that when ICOS+PD-1(+)Tfh cells were used in combination with PD-1(+)Tfh cells, the diagnostic efficacy in distinguishing active UC from stable remission patients was higher than that of any one used alone, with area under curve (AUC) value 0 center dot 931. Our findings suggest that increased ICOS+PD-1(+)Tfh cells are associated with the activation of B cells in the pathogenesis of UC, and may be a potential biomarker for UC disease monitoring.